Biomaterials are synthetic or natural materials that function in intimate contact with living tissue. Biomaterials may be applied to the surface of a tissue to form a tissue surface, or they may be applied to the surface of a medical device, sensor, or implant. Synthetic biomaterials comprising hydrophilic polymers (hydrogels) are favorable because water associates with the water-soluble polymer, and the structure of the water around the polymer hinders protein adsorption.
Because of their ability to be in intimate contact with tissue, several attempts have been made to produce thinly layered, durable biomaterials that can be utilized to deliver a drug in vivo. But producing a thinly layered biomaterial suitable for drug delivery has proven to be a challenge. Several thinly layered biomaterials have been produced, but are not utilized for drug delivery. For example, thin polymer films comprising multiple layers of polyelectrolytes linked non-covalently have been formed and stabilized by chemical cross-links. Thin polymer films comprising multiple layers of covalently cross-linked hydrophilic polymers have also been formed layer-by-layer.
Attempts have been made to include proteins in biomaterials to function as drug carrying agents. Proteins, for example, have been cross-linked with hydrophilic polymers to form thick hydrogels (U.S. Pat. No. 5,733,563). Drugs or enzymes have been added to thick PEG/albumin hydrogels (Journal of Artificial Cells, Blood Substitutes, and Immobilization Biotechnology 1995, 23, 605-611; Biotechnology Applied Biochemistry 2001, 33, 201-207). It is difficult, however, to form certain surface coatings with these thick hydrogels. Additionally, it is difficult to achieve controlled drug release with these thick hydrogels. A need, therefore, remains for both thick and thinly layered biomaterials having proteins that can be utilized to deliver drugs in vivo.